Acute behavioral effects and abuse potential of trazodone, zolpidem and triazolam in humans

• Published in: Psychopharmacologia 1999-06, Vol.144 (3), p.220-233
• Main Authors: RUSH, C. R, BAKER, R. W, WRIGHT, K
• Format: Article
• Language: English
• Subjects: Adult; Antidepressants; Antidepressive Agents, Tricyclic - adverse effects; Antidepressive Agents, Tricyclic - pharmacology; Benzodiazepines; Biological and medical sciences; Drug abuse; Drug dosages; Drug toxicity and drugs side effects treatment; Humans; Hypnotics; Hypnotics and Sedatives - adverse effects; Hypnotics and Sedatives - pharmacology; Male; Medical sciences; Memory - drug effects; Mental Recall - drug effects; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacokinetics; Pharmacology. Drug treatments; Postural Balance - drug effects; Psychomotor Performance - drug effects; Pyridines - adverse effects; Pyridines - pharmacology; Sleep disorders; Substance-Related Disorders - etiology; Surveys and Questionnaires; Time Factors; Trazodone - adverse effects; Trazodone - pharmacology; Triazolam; Triazolam - adverse effects; Triazolam - pharmacology; Zolpidem
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130050997

The present study examined the acute behavioral effects and abuse potential of three drugs commonly used to treat sleep disorders, trazodone, zolpidem and triazolam, and placebo in ten male volunteers with histories of alcohol and drug abuse. Trazodone (100, 200 and 300 mg), a triazolopyridine antidepressant, was included because antidepressants are being used more frequently to treat sleep disorders, but it is unclear whether they have a distinct behavioral pharmacologic profile relative to benzodiazepine hypnotics. Zolpidem (15, 30 and 45 mg), an imidazopyridine hypnotic, was tested because it is the most commonly prescribed hypnotic and purportedly has a unique benzodiazepine-receptor binding profile. Triazolam (0.25, 0.5 and 0.75 mg), a triazolobenzodiazepine hypnotic, was included as the standard component because previous laboratory studies have demonstrated that it has at least some abuse potential. Trazodone, zolpidem and triazolam generally produced comparable dose-related increases in scores on the PCAG scale of the ARCI, which suggests the doses tested were equivalent on some behavioral dimension. The effects of trazodone on subject-rated items thought to measure abuse potential (e.g., subject ratings of Willing to Take Again) were less than those observed with triazolam. Zolpidem and triazolam produced comparable effects on these measures. The highest dose of zolpidem, but not triazolam, increased ratings of Like Drug, Happy, Good Effects, Friendly, Elated, Carefree and Bad Effects. Triazolam and zolpidem produced dose-dependent impairment on all of the performance tasks. Trazodone impaired performance on some, but not all, of these tasks. Consistent with the pharmacokinetics of these compounds, the time-action functions of trazodone, zolpidem and triazolam were similar on these measures. These data suggest that trazodone has less abuse potential than triazolam, and may be a viable alternative to benzodiazepine hypnotics in individuals with histories of alcohol or drug abuse. By contrast, despite its unique neuropharmacological profile, the acute behavioral effects and abuse potential of zolpidem are comparable to those of triazolam.